Oral administration of a nontoxic strain of Clostridium difficile may significantly reduce the likelihood of C. difficile infection returning for some patients treated for the condition. This is according to a new study published in JAMA.
C. difficile infection is at an all-time high in the US. There were almost half a million cases in 2011, with around 29,000 of these resulting in death within 30 days of diagnosis.
The bacterium is the most common cause of health-care associated infection in hospitals in the US, with elderly patients and those taking antibiotics at highest infection risk.
For some patients, C. difficile infection can be treated simply by halting the use of antibiotics. Most commonly, however, treatment involves oral administration of other antibiotics, such as vancomycin or metronidazole.
But according to study author Dr. Dale N. Gerding, of the Edward Hines Jr. VA Hospital in Hines and Loyola University Chicago – both in Illinois – and colleagues, C. difficile infection returns in around 25-30% of patients who receive such treatment.
The team notes, however, that not all strains of C. difficile are harmful, and past studies have shown that nontoxic strains of the bacterium may actually protect against C. difficile infection.
To investigate further, Dr. Gerding and colleagues conducted a phase 2 randomized controlled trial involving 173 patients aged 18 and older who had been diagnosed with either a primary or recurrent C. difficile infection.
All patients had been successfully treated with either metronidazole, oral vancomycin or both.
For the study, the patients were randomly assigned to receive one of four different treatments: an oral liquid formulation of nontoxic C. difficile strain M3 (NTCD-M3) at 104 daily for 7 days, NTCD-M3 at 107 spores daily for 7 days, (NTCD-M3) at 104 daily for 14 days, or a placebo for 14 days. The team reports that 157 patients completed their treatment regimens.
They found that recurrence of C. difficile infection was significantly lower among patients treated with either NTCD-M3 regimen compared with those who received the placebo, at 11% vs 30%. The lowest recurrence rate was among patients who received NTCD-M3 at 107 spores daily for 7 days, at 5%.
What is more, the team identified high rates of fecal colonization among patients treated with NTCD-M3, and this colonization correlated with lower recurrence of C. difficile infection.
Thirty-one percent of patients who received NTCD-M3 but who did not experience fecal colonization had recurrent C. difficile infection, compared with only 2% of NTCD-M3-treated patients with fecal colonization.
The team found treatment with NTCD-M3 was generally well tolerated. Diarrhea or abdominal pain was experienced by 46% and 17% of these patients, respectively, while 60% of patients who received the placebo reported diarrhea and 33% reported abdominal pain.
Adverse side effects were reported in 7% of placebo patients and 2% of NTCD-M3 patients. Headache was more common in NTCD-M3 patients, however, affecting 10% compared with 2% of those who received the placebo.
Commenting on their findings, the researchers write:
“Among patients with C. difficile infection who clinically recovered following treatment with metronidazole or vancomycin, oral administration of spores of NTCD-M3 was well tolerated and appeared safe. The NTCD-M3 strain colonized the gastrointestinal tract and significantly reduced C. difficile infection recurrence.”
Though the researchers are unable to explain exactly why NTCD-M3 appears to protect against recurrence of C. difficile infection, they hypothesize that the colonization of this strain may protect against the effects of toxic C. difficile strains.
“The most likely hypothesized mechanism of action of NTCD-M3 is that it occupies the same metabolic or adherence niche in the gastrointestinal tract as does toxigenic C. difficile and, once established, is able to outcompete resident or newly ingested toxigenic strains,” they explain.
The authors note that a major limitation of their study is the small sample size and stress that larger studies are needed to confirm their findings.
In March, Medical News Today reported on a study claiming that fecal transplantation for C. difficile may be more effective than previously thought.
The researchers of that study found that the procedure – which involves removing “friendly” bacteria from the feces of a healthy donor and transplanting it into gut of patients with C. difficile infection – normalized patients’ gut bacteria immediately and that this effect lasted for up to 21 weeks.